CRCNS US-France Research Proposal: Probing the Dorsolateral Prefrontal Cortex and Central Executive Network for Improving Neuromodulation in Depression

CRCNS 美法研究提案：探索背外侧前额叶皮层和中央执行网络以改善抑郁症的神经调节

• 批准号: 10612989
• 负责人: Corey J Keller
• 金额: $ 23.15万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10612989
• 关键词: Affect; Algorithms; American; Atlases; Axon; Behavior; Brain; Brain Diseases; Brain region; Cephalic; Clinic; Clinical; Complex; Databases; Decision Making; Depressed mood; Development; Disease remission; Double-Blind Method; Electrophysiology (science); Epilepsy; Evoked Potentials; Exhibits; France; Frequencies; Functional disorder; Future; Goals; Guidelines; Human; Impairment; Implant; Individual; Instruction; Knowledge; Link; Location; Magnetic Resonance Imaging; Major Depressive Disorder; Maps; Measures; Mental Depression; Mental disorders; Methodology; Methods; Modeling; Neurons; Operative Surgical Procedures; Outcome; Parietal; Parietal Lobe; Pathologic; Patients; Pharmaceutical Preparations; Physiology; Population; Prefrontal Cortex; Property; Research Proposals; Resistance; Scalp structure; Signal Transduction; Specificity; Structure; Techniques; Testing; Time; Work; biophysical model; brain behavior; brain dysfunction; clinical predictors; cognitive control; depressed patient; effective therapy; frontal lobe; improved; individualized medicine; innovation; insight; inter-individual variation; interest; nervous system disorder; neural; neural correlate; neuropsychiatric disorder; neuroregulation; novel; prospective; prospective test; repetitive transcranial magnetic stimulation; response; tool

The overarching goal of this work is to improve treatments of medication-resistant neuropsychiatric diseases with repetitive transcranial stimulation (rTMS) by tailoring the target to an individual's brain networks. We are indeed in critical need of these individualized treatments for mental health disorders, which affect nearly 50% of Americans during our lifetimes, and brain stimulation treatments, including rTMS represent innovative approaches for these patients. To alleviate depression, rTMS attempts to target a region of the prefrontal cortex generally located within the central executive network (CEN), which drives decision making, cognitive control, and is critically impaired in depression. However, rTMS is delivered without targeting an individual's CEN, and as such may inadvertently deliver stimulation outside the CEN. This application is motivated by recent developments in the field, including a large-scale whole-brain connectivity database derived from invasive recordings and the demonstration that rTMS in depressed patients induces brain changes that predict clinical improvement. In this proposal, we combine non- invasive TMS studies in healthy subjects and depressed patients with invasive direct stimulation studies from surgical patients. We test the hypothesis that the CEN connectivity is weakened in depression and can be maximally modulated by individualizing localization. The project consists of three aims: (1) investigate the excitability, connectivity, and neuronal properties within the CEN using direct brain recordings in surgical patients with epilepsy; (2) derive accurate TMS tools to measure CEN connectivity non-invasively in healthy and depressed populations; and (3) in a depressed population characterize inter-individual variability within the CEN and prospectively test if localization with TMS at the individual level more effectively modulates this brain network. This approach, which can be generalized to any brain region and disorder, utilizes a large database of direct brain recordings to map a brain network at an unparalleled level of detail, develops a link to direct brain recordings in order to yield validated non-invasive brain measures, and applies these insights to individually localize the network and improve targeted brain stimulation. Scientific outcomes include: (1) the first causal, functional map of the human CEN from direct brain recordings; (2) novel non-invasive brain measures of connectivity grounded in electrophysiology; (3) causal brain signatures of depression in the CEN; (4) a methodology to target an individual's CEN in the clinic; and (5) improved modulation of the CEN using this methodology. In summary, a successful outcome of the proposed work would yield an algorithm and guidelines for personalized TMS targeting based on fully validated brain signatures in depression. RELEVANCE (See instructions): Brain stimulation for depression targets the central executive network (CEN), involved in decision making and cognitive control, core in depression, and difficult to target in the clinic. Here we propose to study the connectivity of the CEN using a combination of invasive and non-invasive brain recordings; we will 1) investigate CEN connectivity from direct brain recordings, 2) derive accurate and causal tools to measure CEN connectivity non- invasively in healthy and depressed populations, and 3) test if CEN localization at the individual level can more effectively modulate this network. A successful outcome of the proposed work would yield an algorithm and guidelines for personalized TMS targeting based on fully validated brain signatures in depression.

这项工作的总体目标是改善与药物抗药性神经精神疾病的治疗 通过将目标定制到个人的大脑网络中，重复的经颅刺激（RTMS）。我们确实在 这些对精神健康疾病的个性化治疗的迫切需要，这影响了近50％的美国人 在我们的一生中，包括RTM在内的大脑刺激治疗代表了这些方法的创新方法 患者。为了减轻抑郁症，RTMS试图针对通常位于前额叶皮层的区域 中央执行网络（CEN）推动决策，认知控制，并受到严重损害 沮丧。但是，RTM的交付而不针对个人的CEN，因此可能会无意中 在CEN外提供刺激。该应用程序是由于该领域的最新发展所激发的，包括 从入侵记录得出的大规模全脑连接数据库和RTMS的演示 在抑郁症中，患者会引起大脑变化，以预测临床改善。在此提案中，我们结合了非 - 来自健康受试者和抑郁患者的侵入性TMS研究。 外科患者。我们检验了CEN连通性在抑郁症中弱化的假设，可以是 通过个体化定位来最大程度地调节。该项目由三个目标组成：（1）调查 使用手术患者的直接脑记录CEN内的兴奋性，连通性和神经元特性 癫痫； （2）在健康和抑郁症中得出准确的TMS工具，以测量CEN连接性 人口； （3）在沮丧的人群中，表征了CEN内的个体间变异性和 前瞻性测试在单个层面上使用TMS定位是否会更有效地调节该大脑网络。这 可以推广到任何大脑区域和混乱的方法，它利用了大脑的大数据库 记录以无与伦比的细节绘制大脑网络，开发到直接脑记录的链接 为了产生经过验证的非侵入性脑测量，并应用这些见解来单独定位网络 并改善目标大脑刺激。科学结果包括：（1）第一个因果关系图 直接脑记录的人类cen； （2）建立在 电生理学； （3）CEN抑郁症的因果脑签名； （4）针对个人的方法 诊所的CEN； （5）使用此方法改善了CEN的调制。总而言之 拟议工作的结果将产生基于个性化TMS的算法和指南 抑郁症中充分验证的大脑签名。 相关性（请参阅说明）： 抑郁症的大脑刺激针对中央执行网络（CEN），参与决策和 认知控制，抑郁症的核心，难以靶向诊所。在这里，我们建议研究连通性 使用侵入性和非侵入性脑记录的组合；我们将1）调查CEN 直接大脑记录的连通性，2）得出准确和因果工具，以测量CEN连接性非 - 在健康和沮丧的人群中侵入式，3）测试CEN在单个级别的定位是否可以更多 有效地调节该网络。拟议工作的成功结果将产生算法，并且 个性化TMS针对抑郁症的大脑签名的个性化TMS指南。